Aging-associated reduction of chromosomal histones in mammalian oocytes

During fetal development, mammalian oocytes complete DNA replication, followed by a long-term cell cycle arrest that can last for almost the entire reproductive lifespan. This prolonged arrest poses a challenge to oocytes in maintaining replication-dependent chromosomal proteins. In this study, we show that chromosomal histones are reduced with age in mouse oocytes. Both types of histone H3 variants, replication-dependent H3.1/H3.2 and -independent H3.3, decrease with age. Aging-associated histone reduction is associated with transcriptomic features that are caused by genetic depletion of histone H3.3. Neither the genetic reduction of chromosomal H3.1/H3.2 nor H3.3 accelerates the aging-associated increase in chromosome defects that cause meiotic segregation errors. We suggest that aging-associated reduction of chromosomal histones is linked to several transcriptomic abnormalities, but does not significantly contribute to errors in meiotic chromosome segregation during the reproductive lifespan of mice.